Posted on 10 February 2020
Chronic inflammation is a key driver of many diseases of ageing, including cancer, atherosclorosis and neurodegenerative diseases. It occurs when inflammation, an important defensive mechanism against pathogens, is constantly triggered by endogenous factors and cannot be resolved. There is therefore great interest in finding ways to target chronic inflammation.
Research from the University of California has uncovered a ‘molecular switch’ for one of the drivers of chronic inflammation, the NLRP3 inflammasome. NLRP3 is a pattern recognition receptor: a molecule that can recognise the presence of potential pathogens and trigger inflammation. When NLRP3 is activated, it assembles with other NLRP3 molecules into a larger complex called an inflammasome.
The inflammasome has been linked to chronic conditions such as cancer. Here, researchers found that when NLRP3 is deacetylated (essentially the removal of a small part of the molecule), inflammasome formation is prevented. When mice had their immune systems replaced by cells that only made deacetylated NLRP3, their insulin sensitivity is improved over time. This suggests that targeting the inflammasome’s molecular switch could help reverse the course of certain ageing diseases, such as some metabolic diseases. However, there is a long way to go before any applications for human treatment are seen.
I think this finding has very important implications in treating major human chronic diseases. It’s also a timely question to ask, because in the past year, many promising Alzheimer’s disease trials ended in failure. One possible explanation is that treatment starts too late, and it has gone to the point of no return. So, I think it’s more urgent than ever to understand the reversibility of aging-related conditions and use that knowledge to aid a drug development for aging-related diseases.Danica Chen, associate professor of metabolic biology, nutritional sciences and toxicology at UC Berkeley
An Acetylation Switch of the NLRP3 Inflammasome Regulates Aging-Associated Chronic Inflammation and Insulin Resistance: https://doi.org/10.1016/j.cmet.2020.01.009
Molecular 'switch' reverses chronic inflammation and aging: https://medicalxpress.com/news/2020-02-molecular-reverses-chronic-inflammation-aging.html